This invention relates to novel pharmaceutical compositions having therapeutic and prophylactic effects in disease conditions involving calcium phosphate metabolism. The invention further relates to a novel method for treating or preventing certain pathological conditions in animals.
A number of pathological conditions which can afflict warm-blooded animals are characterized by anomalous mobilization of calcium and phosphate leading to general or specific bone loss and/or excessively high calcium and phosphate levels in the fluids of the body. These conditions include osteoporosis, a disease process in which bone hard tissue is lost disproportionately to the development of new hard tissue. Osteoporosis can be subclassified as post-menopausal, senile, drug-induced (e.g., adrenocorticoid as can occur in steroid therapy), disease induced (e.g., arthritic and tumor), etc., however, the manifestations are essentially the same.
Another condition involving anomalous mobilization of calcium and phosphate is Paget's disease (osteitis deformans). In this disease, dissolution of normal bone occurs which is then replaced by soft, poorly mineralized tissue such that the bone becomes deformed from pressures of weight bearing, particularly in the tibia and femur.
Until recently, no satisfactory medical treatment for disease conditions involving anomalous mobilization of calcium phosphates has been provided, although dietary Vitamin D, calcium, fluorides, estrogens, and the hormone calcitonin (thyrocalcitonin) have been suggested on tested for these conditions. More recently it has been discovered that certain phosphonate compounds as hereinafter more fully defined are effective in the treatment of such diseases. The following U.S. patents and applications, for example, are directed to the use of various phosphonates in the treatment of such disease conditions: Francis, U.S. Application Ser. No. 51,355, filed June 30, 1970; U.S. Pat. No. 3,683,080, granted Aug. 8, 1972; U.S. Pat. No. 3,678,164, granted July 18, 1972; U.S. Pat. No. 3,662,066, granted May 9, 1972; U.S. Pat. No. 3,553,314, granted Jan. 5, 1971; U.S. Pat. No. 3,553,315, granted Jan. 5, 1971; U.S. Pat. No. 3,584,124, granted June 8, 1971; U.S. Pat. No. 3,584,125, granted June 8, 1971; and U.S. Pat. No. 3,641,246, granted Feb. 8, 1972.
While the compositions and methods of the foregoing patents and applications constitute an effective treatment for disease conditions such as osteoporosis, higher dosages of these compositions can cause certain adverse physiological responses. For example, higher dosages of such compounds as disodium ethane-1-hydroxy-1,1-diphosphonate can give rise to mineralization defects, i.e., lack of mineralization in mature bone (increased osteoid seams) or inhibition of mineralization of the growth cartilage and/or inhibition of primary spongiosa resorption in the epiphyseal region of bone in rapidly growing animals.